The long term goal of this research program is to understand how eukaryotic DNA replication is regulated during the cell cycle. This question is central to understanding the mechanisms that control cellular proliferation in normal cells, as well as the perturbations of normal growth control that result in cancer. We have chosen Schizosaccharomyces pombe as an experimental system because it has many similarities to higher eukaryotic cells and because it has already proved to be a powerful tool for probing cell cycle control. Our approach involves the use of genetic and biochemical methods to identify and characterize genes that couple the basic cell cycle engine to the initiation of DNA replication. One such gene, cdc18+, appears to play a central role in triggering initiation once each cell cycle and thus, has been a major focus of our work. We expect that information obtained in our studies will complement that obtained from the study of S. cerevisiae and will be directly relevant to the control of DNA replication in higher eukaryotes.